Neuroleptic malignant syndrome

Dopamine is a chemical messenger that controls muscle tone, temperature regulation and parts of the autonomic nervous system. NMS is an idiosyncratic reaction to a sharp fall in dopamine activity in the brain. A recent narrative review describes it as an uncommon but potentially fatal reaction, most often precipitated by antipsychotic drugs, less often by antiemetics, by abrupt withdrawal of dopamine agonists in Parkinson's disease, and by other dopaminergic agents.

The word "malignant" refers to how serious it can become, not to cancer. It is a medicine-related emergency that unfolds over days, and it is unrelated to the longer-term movement problems such as tardive dyskinesia, which develop over months or years.

The NHS tells people taking olanzapine to call 999 or go to A&E for a high temperature, muscle stiffness, sweating, anxiety or excess saliva, naming neuroleptic malignant syndrome as the concern. Relatives and carers often notice the change first, because the person may be too drowsy or confused to report it.

Clinicians look at several features together rather than any single one. The international consensus criteria and the DSM-5 research criteria both require measured hyperthermia, but the review above highlights that this requirement can delay recognition and that rigidity usually precedes fever in people who go on to become feverish.

• Stiff, "lead-pipe" muscles, tremor, difficulty swallowing or very little speech

• Raised temperature, heavy sweating, fast pulse and fast breathing

• Confusion, agitation, drowsiness or reduced responsiveness

• Swinging blood pressure, incontinence or dark urine

• Blood tests showing high creatine kinase and a raised white cell count

Any antipsychotic can be involved, whether it is an older (first-generation) or newer (second-generation) drug, and a published Finnish study found no significant difference by class while a US cohort found higher incidence with first-generation agents. This inconsistency is one reason clinicians treat every dopamine blocker as a possible trigger. Anti-sickness medicines such as metoclopramide also block dopamine.

The reverse can happen in Parkinson's disease: missing doses of levodopa-type medicines in hospital can produce a similar picture. The review also notes that people without a measured fever are often worked up for sepsis, serotonin syndrome or catatonia instead, and during that time the dopamine blocker may be continued.

Because it is so unpredictable, anyone who has had NMS before, or a relative who has, should tell every prescriber and hospital team.

Because NMS overlaps with other emergencies, doctors work in parallel to rule out alternatives rather than waiting for a perfect fit.

The review concludes that withdrawing the offending dopamine blocker (or restarting the withdrawn dopamine medicine) is the only intervention consistently supported across the primary evidence, and that it should not wait for confirmation of fever. Supportive care is the cornerstone: fluids, protecting the kidneys, cooling and monitoring for respiratory failure and muscle breakdown.

Specialist drugs such as bromocriptine and dantrolene, benzodiazepines and electroconvulsive therapy are used selectively. The same review notes that evidence for them is limited and that the only prospective comparative study found that dantrolene or bromocriptine tended to prolong illness compared with supportive care alone. Severe cases are managed in a high-dependency or intensive care setting.

Monitoring includes repeated temperature checks, serial CK, level of consciousness, urine output and kidney function.

Most people who are treated early recover over days to weeks, although the review stresses that the evidence base is observational and conclusions are directional rather than definitive. The kidneys, muscles and lungs are the organs that need follow-up.

A mental health condition that needed antipsychotic treatment does not disappear after NMS, so psychiatrists weigh whether and when another antipsychotic is appropriate, often waiting some time and choosing carefully with close monitoring. NICE guidance on psychosis asks teams to discuss likely side effects of each drug before starting treatment, and a past NMS episode should be written into the record as a serious drug reaction. Suspected reactions can be reported through the MHRA Yellow Card scheme.